A novel approach to immunotherapy of allergy is to use immunostimulatory oligonucleotides (ISS) to up-regulate Th1 and down-regulate Th2 responses to allergens. Preliminary results in mice demonstrate that certain ISS are potent modulators of such responses and are effective in treating respiratory allergy. Unfortunately, while the mouse is a good model for monitoring specific immune responses, it is a poor model for human allergy and asthma. In contrast, respiratory allergy in dogs appears to be very similar to human respiratory allergy and can provide meaningful clinical endpoints to immunotherapy. In the Phase I period of this project, ISS formulations will be tested for their ability to reduce allergic responses upon pulmonary ragweed challenge in sensitized dogs. Immunotherapy with ragweed allergen- ISS conjugate will be tested for induction of Th1-type immune responses (high IgG, low IgE) and reduction of pulmonary allergic symptoms upon challenge in sensitized dogs. If Phase I studies prove positive. Phase II studies would go on to define the optimal ISS formulations, regimens and delivery methods for preventing or treating pulmonary allergic responses to Amb a 1, and longevity of the effects of ISS or ragweed-ISS conjugate in the dog model. PROPOSED COMMERCIAL APPLICATIONS: The goal of this research is to develop novel formulations of allergens and immunostimulatory oligonucleotides that could be used in the prevention or treatment of respiratory allergies and asthma. Proof of feasibility in Phase I would lead to studies to optimize delivery route, dose, formulation, and regimen as well as investigation of correlates of activity in Phase II. Positive results in the dog respiratory allergy model would be important in decisions to move these novel immunotherapy products into clinical testing for treating human pulmonary allergies.